Nonanthracycline Neoadjuvant Regimen Appears Effective and Safe in Stage II/III Breast Cancer

September 1, 2004

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

GYEONGGI, KOREA-Instage II/III breast cancer, neoadjuvantdocetaxel (Taxotere)/capecitabine(Xeloda) (TX) appears to offer improvedclinical and pathologic completeresponse rates vs doxorubicin(Adriamycin)/cyclophosphamide(Cytoxan/Neosar) (AC), preliminaryphase III trial data suggest (abstract607).Tumor response was seen in 91%of evaluable patients on TX vs 74% ofpatients on AC, reported investigatorHong Gi Lee, MD, of the ResearchInstitute and Hospital, National CancerCenter, Goyang, Gyeonggi, Republicof Korea. In addition, pathologiccomplete response (pCR) inprimary tumors was 23% for TX vs6% for AC. A pCR of 23% is "consistentwith best rates reported from otherneoadjuvant trials of doublecombinations," Dr. Lee said."Lack of pathologic complete responseis a surrogate marker of poorsurvival benefit, and our results showthat the docetaxel and capecitabinecombination achieved a pCR higherthan with an anthracycline regimen."The preliminary results come froma trial in which patients with treatment-naive stage II/III breast cancerare randomized to either TX or AC,followed by surgery, then a crossoverto the opposite treatment arm: patientsrandomized to TX preoperativelygo on to receive AC after surgery,whereas patients randomized toAC then receive TX.The rationale for using docetaxel/capecitabine as primary chemothera-py for breast cancer comes from severallines of evidence suggesting benefit.Dr. Lee noted that docetaxel use isincreasing in the primary setting, basedon studies such as the NSABP (NationalSurgical Adjuvant BowelProject) Protocol B-27, which suggestedthat adding docetaxel to ACpreoperatively significantly increasedclinical and pathologic response rates(J Clin Oncol 21:4165-4174, 2003).Capecitabine has been shown to beeffective and well tolerated as a singleagent in metastatic breast cancer, whilethe docetaxel/capecitabine combinationextended survival, response rate,and time to progression in a phase IIItrial by O'Shaughnessy et al. (J ClinOncol 20:2812-2823, 2002).To compare the efficacy and toxicityof AC and TX as primary chemotherapyfor stage II/III breast cancer,Dr. Lee and colleagues enrolled 121patients (mean age 44 years, approximately60% stage II) who had receivedno prior chemotherapy, hormonaltherapy, radiation, or surgery. All patientshad positive axillary lymphnodes and good performance status(ECOG [Eastern Cooperative OncologyGroup] 0 or 1).The preoperative treatment regimenswere given every 3 weeks forfour cycles. The TX arm consisted ofdocetaxel (75 mg/m2 in a 1-hour infusionon day 1) and capecitabine (1,000mg/m2 PO twice daily on days 1-14).The AC arm consisted of doxorubicin(60 mg/m2 IV on day 1) plus cyclophosphamide(600 mg/m2 IV on day1). After surgery, patients crossed overto the opposite arm and received furtherradiation with or without tamoxifen.Interim AnalysisAt ASCO, Dr. Lee presented aninterim analysis on 100 patients whohave completed surgery. Complete orpartial response was higher in TXtreatedvs AC-treated patients (seeTable 1). In the TX arm, 9% had stabledisease vs 17% in the AC arm, in which9% of patients had progressive disease.The TX arm also had increasedpCR vs AC, both in primary tumors(23% vs 6%) and in lymph nodes(34% vs 28%). According to Dr. Lee,TX appeared to be as effective inHER2+ tumors as in HER2- tumors.Tumor and lymph node downstagingwas also reported. Patients on TXhad a 69% reduction in median tumorlength, compared with 45% forAC-treated patients; likewise, therewas an 82% reduction in lymph nodesize for TX, and a 62% reduction forAC. Also, the TX regimen caused lessnausea and vomiting vs AC, but it ledto more myalgia, skin toxicities, andnail changes.Recruitment in this trial is ongoing;according to investigators, finaldata should be available in about 1year. "The final results are awaitedwith interest to determine whether ornot nonanthracycline-based primarytherapy is effective and well-toleratedin stage II/III breast cancer," Dr. Leesaid. This study was supported byAventis Pharma, Roche Korea, and agrant from the National Cancer Center,Korea.